JP4231222B2 - Skin basement membrane application composition - Google Patents

Description

[0001]
[Technical field to which the invention belongs]
The present invention relates to a skin basement membrane utilization composition comprising rice bran oil that promotes the production of laminin 5, which is a constituent of skin basement membrane, as an active ingredient.
[0002]
[Prior art]
Conventionally, it is known that changes caused by skin aging such as wrinkles, blotches, dullness, sagging and the like involve aging, sun exposure, environmental stress, mental stress, and the like. Micro changes inside the skin include decrease and degeneration of elastic fibers such as type I collagen, type III collagen and elastin in the dermis, decrease and degeneration of type IV collagen and laminin in the basement membrane, turnover of epidermal cells An abnormality has occurred.
[0003]
The basement membrane is a dense membrane composed of extracellular matrix proteins such as type IV collagen, laminin, and fibronectin. In the skin, the basement membrane exists at the junction between the epidermis and dermis. It plays an important role in maintaining the structure of the skin, and is involved in the control of epidermal turnover and the transmission of information between the epidermis and the dermis.
[0004]
Laminin 5 is known as a kind of protein having a particularly important function among extracellular matrix proteins constituting the skin basement membrane. Laminin 5 is produced by epidermal cells and is involved in the connection between epidermal cells and the basement membrane, and is also associated with type VII collagen and also in the connection between the dermis and the basement membrane (Rousselle, P., et al., J. Biol. Cell Biol., 114, 567-576, 1991., Rousselle, P., et al., J. Cell Biol., 138, 719-728, 1997., Chen, M., et al., J. Invest. Dermatol., 112, 177-183, 1999). Laminin 5 is normal because abnormalities in the laminin 5 gene cause severe epidermolysis bullosa (Herlitz's junctional epidermolysis bullosa), a severe genetic disease characterized by epidermis-dermis separation and blister formation It is known to be an essential protein for the maintenance of skin structure (Aberdam, D., et al., Nat. Genet., 6, 299-304, 1994., Pulkkinen, L., et al., Genomics, 24, 357-360, 1994., Kiririkko, S., et al., Hum. Mol. Genet., 4, 959-962, 1995.).
[0005]
Recently, skin basement membrane damage such as tearing and multiplexing of the basement membrane has been observed since the early 20s at exposed areas such as cheeks and wrinkles, and it is significantly worsened from the late 20s to the early 30s. These results suggest that basement membrane damage is an important factor in causing skin aging. In addition, it has been shown that purified laminin 5 and substances that promote the production of laminin 5 promote basement membrane formation and are useful substances for basement membrane care {J. Soc. Cosmet. Chem. Jpn. , Review, 35 (1) 1-7, 2001}.
[0006]
In view of the above, in order to prevent skin aging, purified laminin 5 having an action of promoting the formation of a basement membrane and a plant extract or compound that promotes the production of laminin 5 are developed as active ingredients. (JP-A-10-147515, JP-A-11-343226, JP-A-2000-226308, Japanese Patent Application No. 2000-331318, Japanese Patent Application No. 2001-151485).
[0007]
[Problems to be solved by the invention]
However, a composition containing purified laminin 5 as an active ingredient has problems with stability, skin permeability, etc., because laminin 5 is a very high molecular glycoprotein, and a sufficient skin rejuvenating action is expected. Can not. Moreover, it cannot be said that the substance which accelerates | stimulates the production of laminin 5 known until now has sufficient stability and safety, and cannot always expect sufficient skin rejuvenating action. Therefore, development of a component having further excellent stability and safety has been expected.
[0008]
[Means for Solving the Problems]
This inventor examined the effect | action which accelerates | stimulates the production of laminin 5 in an epidermal cell about various components. As a result, rice bran oil was found to promote the production of laminin 5, and the present invention was completed.
[0009]
That is, the present invention provides: 1. Skin basement membrane utilization composition containing rice bran oil; 2. Composition for promoting production of laminin 5 containing rice bran oil; 3. The composition according to 1 or 2, which is used for suppressing light damage. It is related with the composition of 1, 2 or 3 which is an external use for skin.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
The rice bran oil used in the present invention is a semi-drying oil obtained from rice bran just after rice seed milling and is generally commercially available. A pale yellow oily liquid that contains a large amount of free fatty acids, waxes, tocopherols, oryzanols, sterols, trace amounts of phospholipids, glycolipids, metals, etc. in addition to neutral fats. Fatty acid components are mainly oleic acid, linoleic acid, and palmitic acid.
[0011]
It is very stable against air and heat due to the effects of tocopherol and oryzanol. There is almost no toxicity to skin cells such as epidermal cells and fibroblasts, and it is very safe.
[0012]
Oryzanol in rice bran oil has the effect of protecting the skin by absorbing ultraviolet rays. In addition, it has a cholesterol-lowering effect and is used as an edible oil because it has a good touch and good flavor. Rice bran oil fatty acid has a large amount of oleic acid, and soap produced from rice bran oil is easily dissolved in water, has excellent detergency, and is used as a household detergent. Used in Europe and America as a natural sunscreen oil (Cosmetic Handbook, Nikko Chemicals Co., Ltd., Chuo Printing Co., Ltd.).
[0013]
The effective blending amount of the rice bran oil in the composition of the present invention is appropriately selected and determined according to the preparation method of the rice bran oil, the form of the preparation, etc., and is not particularly limited, but is suitably 0.01 to 30% by weight.
[0014]
The composition of the present invention containing rice bran oil promotes the production of laminin 5 in epidermal cells, is useful for promoting the activation and regeneration of the skin basement membrane, and enhances the action of the skin basement membrane that has been reduced by irradiation with ultraviolet rays. Strengthens the binding force between the basement membrane and basal cells and has a so-called photoaging regeneration effect.
[0015]
The composition of the present invention includes fats and oils such as vegetable oils, higher fatty acids, higher alcohols, silicones, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, preservatives, sugars, metals Contains a sequestering agent, a polymer such as a water-soluble polymer, a thickener, a powder component, a UV absorber, a UV blocker, a moisturizer such as hyaluronic acid, a fragrance, a pH adjuster, a desiccant, etc. be able to. Vitamins, skin activators, blood circulation promoters, resident bacteria control agents, active oxygen scavengers, anti-inflammatory agents, anticancer agents, whitening agents, bactericides, and other medicinal components and physiologically active components can also be included.
[0016]
Examples of oils and fats include camellia oil, evening primrose oil, macadamia nut oil, olive oil, rapeseed oil, corn oil, sesame oil, jojoba oil, germ oil, wheat germ oil, glycerin trioctanoate, and the like, cocoa butter, coconut oil, Hardened coconut oil, palm oil, palm kernel oil, owl, owl kernel oil, hardened oil, hardened castor oil, etc. Waxes.
[0017]
Examples of hydrocarbons include liquid paraffin, squalene, squalane, and microcrystalline wax.
[0018]
Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the like.
[0019]
Examples of the higher alcohol include linear alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, and cetostearyl alcohol, and branched chain alcohols such as monostearyl glycerol ether, lanolin alcohol, cholesterol, phytosterol, and octyldodecanol.
[0020]
Examples of silicone include linear polysiloxanes such as dimethylpolysiloxane and methylphenylpolysiloxane, and cyclic polysiloxanes such as decamethylcyclopentasiloxane.
[0021]
Examples of the anionic surfactant include fatty acid salts such as sodium laurate, higher alkyl sulfates such as sodium lauryl sulfate, alkyl ether sulfates such as POE lauryl sulfate triethanolamine, N-acyl sarcosine acid, sulfosuccinate , N-acylamino acid salts and the like.
[0022]
Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride, benzalkonium chloride, and benzethonium chloride.
[0023]
Examples of amphoteric surfactants include betaine surfactants such as alkyl betaines and amide betaines.
[0024]
Examples of nonionic surfactants include sorbitan fatty acid esters such as sorbitan monooleate and hydrogenated castor oil derivatives.
[0025]
Examples of preservatives include methyl paraben and ethyl paraben.
[0026]
Examples of the sequestering agent include edetates such as disodium ethylenediaminetetraacetate, edetic acid, and sodium edetate.
[0027]
Examples of the polymer include gum arabic, gum tragacanth, galactan, guar gum, carrageenan, pectin, agar, quince seed, dextran, pullulan carboxymethyl starch, collagen, casein, gelatin methylcellulose, methylhydroxypropylcellulose, hydroxyethylcellulose, sodium carboxymethylcellulose ( CMC), vinyl polymers such as sodium alginate carboxyvinyl polymer (such as CARBOPOL), and the like.
[0028]
Examples of the thickener include carrageenan, tragacanth gum, quince seed, casein, dextrin, gelatin, CMC, hydroxyethyl cellulose, hydroxypropyl cellulose carboxyvinyl polymer, guar gum, xanthan gum, bentonite and the like.
[0029]
As the powder component, talc, kaolin, mica, silica, zeolite, polyethylene powder, polystyrene powder, cellulose powder, inorganic white pigment, inorganic red pigment, titanium oxide coated mica, titanium oxide coated talc, colored titanium oxide coated mica, etc. Mention may be made of organic pigments such as pearl pigments, red 201 and red 202.
[0030]
Examples of the ultraviolet absorber include paraaminobenzoic acid, phenyl salicylate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2,4-dihydroxybenzophenone, and the like.
[0031]
Examples of the ultraviolet blocking agent include titanium oxide, talc, carmine, bentonite, kaolin, and zinc oxide.
[0032]
As humectants, polyethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,2-pentanediol, glycerin, diglycerin, polyglycerin, xylitol, maltitol, maltose, sorbitol, glucose, fructose, chondroitin Examples thereof include sodium sulfate, sodium hyaluronate, sodium lactate, pyrrolidone carboxylic acid, cyclodextrin and the like.
[0033]
The medicinal properties include vitamin A oil, vitamin A such as retinol, vitamin B ₂ such as riboflavin, B ₆ such as pyridoxine hydrochloride, L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid Vitamin C such as monopalmitate, L-ascorbic acid dipalmitate, L-ascorbic acid-2-glucoside, pantothenic acid such as calcium pantothenate, vitamin D such as vitamin D ₂ and cholecalciferol; α -Vitamins, such as vitamin E, such as tocopherol, tocopherol acetate, and DL-α-tocopherol nicotinate. Whitening agents such as placenta extract, glutathione, and Yukinosita extract, skin activators such as royal jelly, beech extract, capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, blood circulation promoters such as γ-oryzanol, glycyrrhizic acid Derivatives, glycyrrhetinic acid derivatives, anti-inflammatory agents such as azulene, amino acids such as arginine, serine, leucine and tryptophan, maltose sucrose condensates of resident bacteria control agents, lysozyme chloride and the like. In addition, chamomile extract, parsley extract, beech extract, wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, loquat extract, buckwheat extract, yakuinin extract, assembly extract, merirot extract, birch extract, licorice extract , Peony extract, bonito extract, loofah extract, capsicum extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, seaweed extract, cucumber extract, clove extract, carrot extract, Examples include various extracts such as maroni extract, hamamelis extract and mulberry extract.
[0034]
The composition of the present invention can be applied in the form of a solid agent such as an aqueous solution, oil agent, emulsion, suspension or other semi-solid agent such as gel or cream, powder, granule, capsule, microcapsule or solid. is there. It is prepared in these forms by conventionally known methods, and lotions, emulsions, gels, creams, ointments, plasters, haps, aerosols, suppositories, injections, powders, granules, tablets, pills , Various dosage forms such as syrups and lozenges. These can be applied to the body by applying, sticking, spraying, drinking and the like. Among these dosage forms, lotions, emulsions, creams, ointments, plasters, haptics, aerosols and the like are particularly suitable for external preparations for skin. Cosmetics include skin lotions such as lotions, emulsions, creams, packs, makeup base lotions, makeup creams, emulsions, cream-like or ointment-type foundations, lipsticks, eye colors, and cheek colors. Preparations, body creams such as hand creams, leg creams and body lotions, bath preparations, oral cosmetics, and hair cosmetics.
[0035]
【Example】
EXAMPLES Next, although an Example is given and this invention is further demonstrated, this invention is not limited to these Examples.
[0036]
Test results 1. Measurement of Laminin 5 Production Promoting Action in Human Skin Three-Dimensional Model The human skin three-dimensional model was cultured using TESTSKIN (LSE-high) (Toyobo) according to the protocol. Fetal bovine serum (FBS) or rice bran oil (Tsukino Food Industry) was dissolved in plant squalane (Kao), and 80 μl was added to the tissue in the assay ring and cultured for 24 hours. FBS is a known substance that promotes the production of laminin 5, and was used here as a control (Japanese Patent Laid-Open No. 11-343226). After washing with the culture solution several times to completely remove the drug, UVB was irradiated at 0 and 240 mJ / cm ² . The drug was newly added and further cultured for 24 hours. The tissue was recovered, and a tissue extraction solution {50 mM Tris-HCl (pH 7.5), 1% (Octylphenoxy) polyethylethanol (Sigma-Aldrich)} was added and homogenized. The tissue piece was removed by centrifugation at 15,000 rpm for 30 minutes, and dialyzed against 50 mM Tris-HCl (pH 7.5).
[0037]
Using this tissue extract, laminin 5 production promoting action was examined by ELISA (enzyme-linked immunosorbent assay). The tissue extract was appropriately diluted with 50 mM Tris-HCl (pH 7.5) and adsorbed on a 96-well ELISA plate at 4 ° C. for 18 hours. After removing the cell culture supernatant, the cells were immersed in a blocking solution {PBS (−) containing 1% bovine serum albumin (BSA)} and blocked at 37 ° C. for 1 hour. After washing with a washing solution {PBS (-)} containing 0.05% polyoxyethylene (20) sorbitan monolaurate (Wako Pure Chemical Industries, Ltd.)}, the primary antibody solution {for laminin γ2 chain prepared to 5 mg / ml with the washing solution Monoclonal antibody (clone D4B5) (Mizushima, H., et al., Horm. Res., 50, 7-14, 1998.)} was added and reacted at 37 ° C. for 2 hours. After washing, a secondary antibody {biotinylated anti-mouse immunoglobulin G (Vector laboratories) prepared to 1 mg / ml with a washing solution} was added and reacted at room temperature for 1 hour. After washing, an enzyme solution {alkaline phosphatase avidin D (Vector laboratories) prepared to 1 mg / ml with a washing solution} was added and reacted at room temperature for 1 hour. After washing, a substrate solution {0.75 M Tris-HCl (pH 10.3) containing 1 mg / ml p-nitrophenyl phosphate (ICN Biomedicals, Inc.)} was added, reacted at 37 ° C. for 30 minutes, and then at 405 nm. Absorbance was measured.
[0038]
The results when treated with 1.0% FBS and 0.1%, 1.0% and 3.0% rice bran oil are shown in FIG. Here, “treating FBS at 1.0%” means adding a stock solution of FBS to plant squalane at 1.0%. Also, treating rice bran oil with 0.1%, 1.0% and 3.0% means adding the stock solution of rice bran oil to plant squalane at 0.1%, 1.0% and 3.0%, respectively. Processing. Evaluation was made with the drug untreated and UVB unirradiated as 100%. As a result, rice bran oil promoted laminin 5 production in a concentration-dependent manner in both non-UVB irradiation and irradiation. In addition, the production of laminin 5 was similarly promoted when FBS was treated.
[0039]
Test result 2. Measurement of Photodamage Inhibitory Effect in Human Skin Three-Dimensional Model Human skin three-dimensional model was cultured according to the protocol using TESTSKIN (LSE-high). FBS or rice bran oil was dissolved in plant squalane, and 80 μl was added onto the tissue in the assay ring, and cultured for 24 hours. After washing with the culture solution several times to completely remove the drug, UVB was irradiated at 0 and 240 mJ / cm ² . The drug was newly added and further cultured for 24 hours, and then the tissue culture solution was collected and centrifuged at 15,000 rpm for 30 minutes to remove tissue pieces.
[0040]
Cytotoxicity was measured by measuring lactate dehydrogenase (LDH) activity released from cells damaged by the cell membrane using this tissue culture solution. The LDH activity was measured using an LDH-cytotoxicity test kit (Wako Pure Chemical Industries). A tissue culture solution appropriately diluted with PBS (-) was dispensed into a 96-well reaction plate, and then the color developing solution was treated and reacted at room temperature for 20 minutes. After processing the reaction stop solution, the absorbance at 560 nm was measured with a microplate reader to evaluate cytotoxicity.
[0041]
The results when treated with 1.0% FBS and 0.1%, 1.0% and 3.0% rice bran oil are shown in FIG. The cytotoxicity rate when the drug was not treated and UVB was not irradiated was evaluated as 100%. In the case of non-irradiation with UVB, the cytotoxicity rate was almost the same regardless of the presence or absence of the drug treatment. On the other hand, when UVB was irradiated, the cytotoxic rate increased about twice as compared with the untreated, but when treated with rice bran oil, the cytotoxic rate decreased in a concentration-dependent manner. In addition, when FBS was treated, the cytotoxicity rate similarly decreased.
[0042]
Below, the formulation example of this invention is shown.
Formulation Example 1 Cream A cream was produced according to the following formulation (unit: mass%).
(1) Stearyl alcohol 6.0%
(2) Stearic acid 2.0%
(3) Hydrogenated lanolin 4.0%
(4) Squalane 9.0%
(5) Octyldodecanol 10.0%
(6) POE (25) cetyl alcohol ether 3.0%
(7) Glycerin monostearate 2.0%
(8) Rice bran oil 1.0%
(9) Preservative appropriate amount (10) perfume appropriate amount (11) 1,3 butylene glycol 6.0%
(12) PEG 1500 4.0%
(13) Purified water Residue The above components (1) to (10) are heated and dissolved at 80 ° C. to obtain an oil phase. Ingredients (11) to (13) are heated and dissolved at 70 ° C. to obtain an aqueous phase. The aqueous phase was gradually added to the oil phase to emulsify, cooled to 40 ° C. with stirring, and further cooled to 30 ° C. with stirring to obtain a cream.
[0043]
Formulation Example 2 Tablets Tablets were produced according to the following formulation (unit: mass%).
(1) Rice bran oil 20.0%
(2) Lactose 65.0%
(3) Corn starch 14.0%
(4) Guar gum 1.0%
[0044]
【The invention's effect】
As described above, the composition of the present invention containing rice bran oil promotes the production of laminin 5 in epidermal cells, and promotes structure maintenance and functional improvement of the skin basement membrane. Therefore, youthful skin without wrinkles, blemishes, dullness and sagging by preventing, preventing, and improving structural changes and functional deterioration of the skin basement membrane against aging skin, especially skin damaged by ultraviolet rays. Can be maintained.
[Brief description of the drawings]
FIG. 1 is a diagram showing the expression level of laminin 5 when a human skin three-dimensional model is treated with FBS and rice bran oil.
FIG. 2 is a diagram showing the suppression of light damage when a human skin three-dimensional model is treated with FBS and rice bran oil.

Claims (3)

Rice bran oil (excluding the pigmented rice rice bran oil) production promoter of laminin-5, including a. The production promoter for laminin 5 according to claim 1 , which is used for suppressing light damage. The production promoter for laminin 5 according to claim 1 or 2 , which is for external use on the skin.

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